Programmed cell death is a normal and necessary part of mammalian development. For example, the development of separate fingers in a human fetus requires the programmed cell death of tissue between the developing fingers. The biochemical processes that cause programmed cell death may be triggered, however, by a variety of diseases and injuries. For example, programmed cell death may be triggered by traumatic injury, stroke, myocardial infarction, organ transplantation, and mesenteric and peripheral vascular disease. The programmed cell death further undermines the health of the injured or diseased organism.
Each of the foregoing types of diseases and injuries typically include some ischemia and reperfusion injury, which occurs when previously interrupted blood flow is restored to living tissue. For example, blockage of a coronary artery may cause cardiac muscle death due to the temporary lack of blood supply to the cardiac tissue. Additional muscle may die when blood flow is restored to the cardiac muscle by the administration of thrombolytic drugs.
Chronic and acute inflammation can also damage or kill living cells in a mammal. For example, the inflammation associated with emphysema causes lung damage over time. Inflammation may trigger programmed cell death, or may damage living tissue by some other mechanism. Accordingly, there is a continuing need for methods and compositions for inhibiting cell death and/or inflammation in a mammal.